PB0784 - Arginine-containing peptides exhibit antiplatelet effects in experimental type-2 diabetes mellitus and metabolic syndrome

Background: Increased platelet aggregation is observed in hyperglycemia, metabolic syndrome, atherosclerosis, other cardiovascular diseases and metabolic disorders. This can complicate the course of the disease and lead to hypercoagulation and thrombotic complications in the organism. The use of antiplatelet drugs can reduce pathologically elevated platelet aggregation. We have previously shown that proline- and glycine-containing peptides exhibit antirhrombotic effect in the organism.

Aims: Study of the effects of peptides Pro-Arg-Gly (PRG) and Arg-Pro-Ply-Pro (RPGP) on ADP-induced platelet aggregation (PA) in experimental type-2 diabetes mellitus (T2DM) and metabolic syndrome (MS) in rats.

Methods: The experiments were carried out on male Wistar rats in accordance with the Helsinki Declaration. T2DM was induced by prolonged administration of 40% glucose solution (intragastrically, 2g/kg, 15 days). MS was caused by a high-calorie diet and 10% glucose ad libitum (6 weeks). After that peptides were intranasally applied to rats for 5-7 days. Control rats received saline. Blood for the ADP-induced PA study was taken 20h after the last peptides application.

Results: The development of T2DM and MS in rats led to disturbances in vascular-platelet haemostasis, which was accompanied by an increase in aggregation by 1.5-2 times vs. normal rats. Animals treatments by all used peptides lead to PA reduce in all experiments. However, with the development of T2DM, PA decreased by 43-57% vs. control after the use of both peptides, whereas in MS conditions - by 27% (PRG) and 52% (RPGP). The maximum effect was possessed by RPGP, the antiplatelet effect of which was manifested in both pathologies.

Conclusion(s): Thus, the studied peptides in the development of T2DM and MS in rats exhibit antiplatelet effect. We believe that proline- and glycine-containing peptides with the addition of arginine to their molecule can be used as antiplatelet agents in conditions of increased functional platelets activity and tendency to thrombosis.